Israel targeted Deif in a July 13 strike that hit a compound on the outskirts of the southern Gaza city of Khan Younis, but the military said for weeks it was working to determine if he died in the blast.
Hamas has denied he was killed.
More than 90 other people, including displaced civilians in nearby tents, were killed in the strike, Gaza health officials said at the time.
In a statement on Thursday, the Israeli military said that "following an intelligence assessment, it can be confirmed that Mohammed Deif was eliminated in the strike".
We can now confirm: Mohammed Deif was eliminated.— Israel Defense Forces (@IDF) August 1, 2024
There was no immediate comment from Hamas.
The Israeli confirmation came a day after an apparent Israeli air strike in Tehran killed Hamas' top political leader, Ismail Haniyeh.
Israel has not confirmed or denied being behind the attack but Iran has vowed retaliation.
Along with Deif and Haniyeh, Israel has vowed to eliminate Hamas' top leader in Gaza, Yehya Sinwar, but he has so far remained elusive.
Israel says Sinwar and Deif were the masterminds of the October 7 attack in which Hamas-led militants rampaged in southern Israeli communities, killing about 1200 people and taking some 250 others hostage.
Deif was one of the founders of Hamas' military wing, the Qassam Brigades, in the 1990s and lead the unit for decades.
Under his command, it carried out dozens of suicide bombings against Israelis on buses and at cafes and built up a formidable arsenal of rockets that could strike deep into Israel and often did.
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